‘Mutations in virus not specific to India’
varying levels in different districts.
How many genomic sequences of SARS-COV2 has India submitted to the Global Initiative on Sharing All Influenza Data (GISAID)?
India has contributed around 226 genomic sequences of SARS-COV-2 so far to the around 25,000 sequences of SARS-COV-2 that have been shared with unprecedented speed via GISAID. A 1,000-genome sequencing initiative has been launched by Department of Biotechnology (DBT), and 500 are being sequenced by the Council of Scientific & Industrial Research (CSIR).
What are the findings? Are there any key mutations in the SARSCOV2 virus causing disease in India?
The key mutations in SARSCOV-2 virus have been found in spike glycoprotein (D614G, G1124V), nucleocapsid (R203K, G204R), RNA dependent RNA Polymerase (P323L) . The circulating viruses in India belong to three major strains. The majority of our samples belong to A2a and about 15% to A3 genotypes. There are a few samples belonging to genotypes B, B1, B4, and A1a. They do not have any mutation that has been reported to be associated with any disease progression or acquisition so far. So, despite the fact that no key mutation specific to India has been found in the virus and it still continues to be an imported virus strain, we cannot afford to be complacent. We have to remain vigilant and continue tracking the virus to identify emerging quasi-species or strains.
How many states have the SARSCOV2 genetic samples been sequenced from? Is there any difference in the strains causing infections across states? Sequences are currently mostly from Kerala, Karnataka, West Bengal, Gujarat and Uttar Pradesh -- most belong to A2a clade, while some belong to A3 and B1 clades. It is too early to detect major differences. We are trying for a systematic study of viral RNA sequence from different zones of India and correlate with disease severity.
What has been the role of government institutions in the Covid-19 response, including diagnostic, drug and vaccine development? The focus is on self-reliance. We have ramped up our capacity for developing indigenous testing kits. From being completely dependent on imports, we now have over 20 indigenous manufacturers with a diagnostic kit production capacity of nearly 50 lakh kits per month getting ready by the end of May. This includes indigenous components and reagents.
The government’s role has been very proactive in supporting innovation for vaccine development, development of cost-effective diagnostic equipment , as well as drug discovery and repurposing. The Covid Consortium, under DBT-BIRAC (Biotechnology Industry Research Assistance Council), has supported 70 projects. Support has been also given to medical devices such as ventilators and equipment such as PPES, N-95 masks etc, and for drugs and vaccine development. Funding start-ups that offer immediate solutions has been fast-tracked.
Some US studies have found hydroxychloroquine to be ineffective against Covid-19? What is India’s experience?
The recent study from New York which failed to find any mortality benefits associated with the use of hydroxychloroquine is a retrospective cohort study. There are several caveats in the study which need to be accounted for. First, the design of the study precludes attribution of the causal effect of the use of hydroxychloroquine on the disease outcomes. Second, the recipients of the drug were already suffering from severe disease, thus making the comparative sample groups unfair. Third, the best effect of hydroxychloroquine based strategy is seen when initiated in the mild to moderate disease stage. Several clinical trials are underway, and once their results are declared, we shall have definite evidence of the effectiveness of hydroxychloroquine.
Several studies are also underway in India, and as the results emerge, we shall be able to provide more insights into the experiences. However, early reports from the pharmacovigilance programme indicate that there are no unexpected spikes of adverse reactions from the use.
What is the progress on the WHO Solidarity Trial in India?
In India, we plan to randomise at least 1,500 Covid-19 patients over five to six months. The trial has been initiated with 46 randomised Covid-19 patients, symptomatic adults who have been recently hospitalized and have not yet received hydroxychloroquine. The nature of care proposed as part of the randomized trial include providing only local standard of care, administering Remdesivir, hydroxychloroquine, Lopinavir / Ritonavir or Lopinavir / Ritonavir with Interferon Beta-1a. So far, around 2,500 people have been randomized globally. Being a five-arm study, large numbers (> 10,000) are required, although there is no cap on sample size. It’s not possible to give timeframe for outcomes as the analysis resulting from these trials is global.
Is the effect of BCG vaccination being studied in India?
BCG vaccination has been found to be an immunomodulator in malignancies and also protects against certain infectious diseases. Several high-income countries, which do not have routine BCG vaccination in childhood, have initiated clinical trials of BCG in highrisk groups, especially in health care workers. Currently, there are two ongoing clinical trials in India. Serum Institute of India (in Pune) is conducting a trial of VPM1002 and Cadila is conducting a trial using mycobacterium indicus pranii. However, we have to keep in mind the fact that India has very high rates of BCG vaccination at birth, and this could be an effect modifier or confounder in the results.